Hematological Adverse Events with Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia: A Systematic Review with Meta-Analysis

• Type of Material: Article
• Authors: Olivia Kronick, Emory University; Xinyu Chen, Emory University; Nidhi Mehra, Emory University; Armon Varmeziar, Emory University; Rachel Fisher, Emory University; David Kartchner, Emory University; Vamsi Kota, Augusta University; Cassie Mitchell, Emory University
• Language: English
• Date: 2023-08-31
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.3390%2Fcancers15174354
• Title of Journal or Parent Work: Cancers
• Volume: 15
• Issue: 17
• Start Page: 4354
• Grant/Funding Information: This research was funded by Georgia Institute of Technology President’s Undergraduate Research Award to N.M.; research funding from Incyte pharmaceuticals to V.K.; NIH grant R21CA232249, Children’s Hospital of Atlanta Aflac pilot grant, National Science Foundation CAREER award 1944247, and Chan Zuckerberg Initiative 253558 to C.M.
• Keywords: chronic myeloid leukemia; personalized medicine; tyrosine kinase inhibitor; Philadelphia chromosome
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

Abstract

Chronic myeloid leukemia (CML) is treated with tyrosine kinase inhibitors (TKI) that target the pathological BCR-ABL1 fusion oncogene. The objective of this statistical meta-analysis was to assess the prevalence of other hematological adverse events (AEs) that occur during or after predominantly first-line treatment with TKIs. Data from seventy peer-reviewed, published studies were included in the analysis. Hematological AEs were assessed as a function of TKI drug type (dasatinib, imatinib, bosutinib, nilotinib) and CML phase (chronic, accelerated, blast). AE prevalence aggregated across all severities and phases was significantly different between each TKI (p < 0.05) for anemia—dasatinib (54.5%), bosutinib (44.0%), imatinib (32.8%), nilotinib (11.2%); neutropenia—dasatinib (51.2%), imatinib (29.8%), bosutinib (14.1%), nilotinib (14.1%); thrombocytopenia—dasatinib (62.2%), imatinib (30.4%), bosutinib (35.3%), nilotinib (22.3%). AE prevalence aggregated across all severities and TKIs was significantly (p < 0.05) different between CML phases for anemia—chronic (28.4%), accelerated (66.9%), blast (55.8%); neutropenia—chronic (26.7%), accelerated (63.8%), blast (36.4%); thrombocytopenia—chronic (33.3%), accelerated (65.6%), blast (37.9%). An odds ratio (OR) with 95% confidence interval was used to compare hematological AE prevalence of each TKI compared to the most common first-line TKI therapy, imatinib. For anemia, dasatinib OR = 1.65, [1.51, 1.83]; bosutinib OR = 1.34, [1.16, 1.54]; nilotinib OR = 0.34, [0.30, 0.39]. For neutropenia, dasatinib OR = 1.72, [1.53, 1.92]; bosutinib OR = 0.47, [0.38, 0.58]; nilotinib OR = 0.47, [0.42, 0.54]. For thrombocytopenia, dasatinib OR = 2.04, [1.82, 2.30]; bosutinib OR = 1.16, [0.97, 1.39]; nilotinib OR = 0.73, [0.65, 0.82]. Nilotinib had the greatest fraction of severe (grade 3/4) hematological AEs (30%). In conclusion, the overall prevalence of hematological AEs by TKI type was: dasatinib > bosutinib > imatinib > nilotinib. Study limitations include inability to normalize for dosage and treatment duration.